Paracrine purinergic signaling determines lung endothelial nitric oxide production.
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Paracrine purinergic signaling determines lung endothelial nitric oxide production. / Kiefmann, Rainer; Islam, Mohammad N; Lindert, Jens; Parthasarathi, Kaushik; Bhattacharya, Jahar.
In: AM J PHYSIOL-LUNG C, Vol. 296, No. 6, 6, 2009, p. 901-910.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Paracrine purinergic signaling determines lung endothelial nitric oxide production.
AU - Kiefmann, Rainer
AU - Islam, Mohammad N
AU - Lindert, Jens
AU - Parthasarathi, Kaushik
AU - Bhattacharya, Jahar
PY - 2009
Y1 - 2009
N2 - Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca(2+) (Ca(2+)cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca(2+)cyt and NO responses in EC. Lung expansion induced Ca(2+)cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca(2+)cyt oscillations to microvascular NO production.
AB - Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca(2+) (Ca(2+)cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca(2+)cyt and NO responses in EC. Lung expansion induced Ca(2+)cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca(2+)cyt oscillations to microvascular NO production.
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - Calcium Signaling physiology
KW - Cytosol metabolism
KW - Microcirculation physiology
KW - Nitric Oxide metabolism
KW - Nitric Oxide Synthase Type III metabolism
KW - Paracrine Communication physiology
KW - Pulmonary Alveoli blood supply
KW - Pulmonary Circulation physiology
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptors, Purinergic P2 genetics
KW - Tyrosine analogs
KW - derivatives
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - Calcium Signaling physiology
KW - Cytosol metabolism
KW - Microcirculation physiology
KW - Nitric Oxide metabolism
KW - Nitric Oxide Synthase Type III metabolism
KW - Paracrine Communication physiology
KW - Pulmonary Alveoli blood supply
KW - Pulmonary Circulation physiology
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptors, Purinergic P2 genetics
KW - Tyrosine analogs
KW - derivatives
M3 - SCORING: Zeitschriftenaufsatz
VL - 296
SP - 901
EP - 910
IS - 6
M1 - 6
ER -